Several arene and alkene oxides are known to react covalently with macromolecules, including nucleic acids, and to transform cells in vitro, suggesting their role as ultimate carcinogens, mutagens, and cytotoxins. We are studying the cytochrome P-450-dependent monooxygenases, which convert unsaturated hydrocarbons to epoxides, and the further metabolism of arene and alkene oxides by soluble fraction glutathione transferases and microsomal epoxide hydrolase in hepatic and extrahepatic tissues. The relative quantitative importance of these metabolic pathways is being studied at various levels of cellular organization (isolated cells, perfused organs, purified enzymes) in an attempt to understand the mechanisms of organ-specific and cell-specific toxicity mediated by compounds metabolized to epoxides.